Late-night eating and melatonin may impair insulin response

Posted on April 2nd 2019 (over 7 years)

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The body's circadian rhythms – the 24-hour cycles of biological, hormonal, and behavioral patterns – are optimized to promote our survival. These rhythms modulate a wide array of physiological processes, including the body's production of hormones that regulate sleep, hunger, and metabolism, ultimately influencing body weight, performance, and susceptibility to disease. Roughly 10 to 40 percent of gene expression in mammals is under circadian control including genes in the brain, liver, and muscle^[1]^[2]. As such, circadian rhythmicity may have profound implications for human healthspan.

A key player in the body's circadian metabolic processes is melatonin, a hormone produced deep within the center of the brain, in the pea-sized pineal gland. Melatonin plays an important role in our physiology by regulating the expression of more than 500 genes, but we rightly think of it as a sleep inducer with its increased production being tied to both our natural sleep time and our light exposure. In fact, the greatest influence on its secretion is light: generally, melatonin levels are low during the day and high during the night.

But melatonin doesn't regulate sleep alone. It sends messages to other parts of the body in preparation for sleep, including the pancreas, where it binds to receptors and signals the temporary (overnight) suppression of insulin production. This wasn't a problem in our pre-industrial past, but in today's environment of 24-hour food availability, it can have far-reaching effects on health. When food consumption regularly occurs outside normal daylight hours, the risk of hyperglycemia – higher than optimal blood glucose levels – increases. Chronic exposure to elevated glucose increases our risk of developing diabetes and other metabolic disorders. But it might also cause brain volume. Studies have shown in an association of even high normal fasting blood glucose associated with losses in the hippocampus and the amygdala, areas involved in memory and cognition. In other words, healthy people without diabetes.

Humans are the only species that disobeys their biological clocks, uncoupling the natural rhythms of light and dark around us. In this brief episode, we learn how restoring our dietary and sleep pattern to one that more closely syncs with those imposed by nature, especially by avoiding eating within 2-3 hours before bed and onset of melatonin production, may improve our health and potentially prolong our healthspan.

This episode features a clip from circadian biologist Dr. Satchin Panda. Click here for the full interview.

Doctor Rhonda Patrick here. When most people think about what raises blood glucose levels, they think about dietary composition or what you eat, and rightfully so. If you eat a meal that consists of highly refined processed sugar lacking a fiber matrix, it will quickly spike your blood glucose levels. However, what most people do not realize is that in addition to what you eat, when you eat is also a very important determinant of your blood glucose levels. Time restricted eating is a topic I've covered a lot. It refers to eating all your meals within a restricted time period, such as 8 to 12 hours, and then fasting for the remaining 12 to 16 hours.

Obviously, time restricted eating has an intermittent fasting component to it, but it also has a circadian component to it because you try and eat all your meals during a time when your metabolism is optimal. Metabolism changes throughout the day. For example, when healthy adults eat identical meals in terms of both their caloric content and macronutrient content for breakfast, lunch and dinner, their postprandial glucose levels are the lowest in the morning after breakfast and the highest in the evening after dinner. Even though the meals are 100% identical. This may have something to do with melatonin, the hormone that's produced from the pineal gland that plays a role in initiating sleep.

If our circadian conditions are optimal, meaning we aren't bathing ourselves in bright blue light before bed, our bodies naturally start to produce melatonin around two to three hours before we go to sleep. Melatonin has been shown to bind to receptors on the pancreas and this signals to the pancreas to stop producing insulin. That means that our blood glucose levels will remain elevated because glucose is not getting taken up into our cells. I previously had a discussion with the expert on time restricted eating, Dr. Satchin Panda, and he discussed how melatonin plays a role in blood glucose regulation.

So this is where it becomes a little bit complicated because as you said, there is day and night transition and we know that in the evening, as our body prepares to sleep, our melatonin level begins to rise and that melatonin usually rises two to three hours before our habitual sleep time. So if somebody is going to bed around 11, then that melatonin is beginning to rise around 9 o' clock. On an average, for some people it might rise around four hours early, and some people it will rise exactly at bedtime. And when melatonin rises, there is new data showing that melatonin can bind to its receptor in pancreas. And this engagement melatonin with the pancreas Receptor essentially tells the pancreas, okay, it's time to sleep, you don't have to bother releasing insulin.

So in that way, what happens if somebody is having a big meal when there is high melatonin? Then there may not be enough insulin released from pancreas and glucose may stay high in the blood circulation for a long time. And this study, these kind of studies came to publication because almost 10 years ago, large genome wide association studies found that people with obesity or diabetes might have a mutation in melatonin receptor. And that was confusing because what is melatonin to do with obesity and diabetes? And you fast forward 10 years, people went back to the drawing board and looked at where the receptor is expressed and what it does when melatonin is engaged. And then they found out that there is this effect of melatonin on insulin.

So that's why people who are eating late into the night, they may not get the best benefit in terms of glucose control because their glucose might remain slightly higher than if they had the same dinner two hours earlier. This is obviously very relevant for people with pre diabetes or type 2 diabetes, but it's also important for the general population. For example, one study showed that people with fasting blood glucose levels between high, normal and slightly pre diabetic may experience more brain atrophy with age. Specifically, they experienced a greater loss in brain volume in the hippocampus and the amygdala regions of the brain that are involved in learning, memory and cognition.

So elevated blood sugar levels, even in the absence of clinically diagnosable type 2 diabetes, may affect brain health. This really drives home the importance of finishing that last meal or anything else that may drive up your blood sugar levels, like that late night glass of wine up to three hours before bed to better align with when our bodies are sending signals to shut down insulin production. I'm Dr. Rhonda Patrick and I'll catch you next time.

Amygdala

An area of the brain located close to the hippocampus, in the frontal portion of the temporal lobe. The amygdala governs our responses to fear, arousal, and emotional stimulation. Poor sleep increases activity within the amygdala.

Blue light

A wavelength of light emitted from natural and electronic sources. Blue light exposure is associated with improved attention span, reaction time, and mood. However, exposure to blue light outside the normal daytime hours may suppress melatonin secretion, impairing sleep patterns. In addition, blue light contributes to digital eye strain and may increase risk of developing macular degeneration.

Circadian rhythms

The body’s 24-hour cycles of biological, hormonal, and behavioral patterns. Circadian rhythms modulate a wide array of physiological processes, including the body’s production of hormones that regulate sleep, hunger, metabolism, and others, ultimately influencing body weight, performance, and susceptibility to disease. As much as 80 percent of gene expression in mammals is under circadian control, including genes in the brain, liver, and muscle.^[1] Consequently, circadian rhythmicity may have profound implications for human healthspan.

^ Dkhissi-Benyahya, Ouria; Chang, Max; Mure, Ludovic S; Benegiamo, Giorgia; Panda, Satchidananda; Le, Hiep D., et al. (2018). Diurnal Transcriptome Atlas Of A Primate Across Major Neural And Peripheral Tissues Science 359, 6381.

View sleep regularity topic

Food matrix

The totality of a food’s structure and composition as it is found in its natural state. A food's matrix may contain vitamins, minerals, fiber, carbohydrates, fats, proteins, secondary metabolites (such as polyphenols), and water. Processing or refining of foods often alters the matrix and may modify a food’s glycemic index. Foods that have a high glycemic index can rapidly produce an elevated glucose response.

GWAS (Genome Wide Association Study)

A type of observational study that searches the genome for small variations, called single nucleotide polymorphisms, or SNPs, that occur more frequently in the DNA of people with a particular disease than in people without the disease. GWAS studies help researchers identify genes that may contribute to a person’s risk of developing a certain disease.

Hippocampus

A small organ located within the brain's medial temporal lobe. The hippocampus is associated primarily with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation. Amyloid-beta plaque accumulation, tau tangle formation, and subsequent atrophy in the hippocampus are early indicators of Alzheimer’s disease.

Insulin

A peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.

Intermittent fasting

A broad term that describes periods of voluntary abstention from food and (non-water) drinks, lasting several hours to days. Depending on the length of the fasting period and a variety of other factors, intermittent fasting may promote certain beneficial metabolic processes, such as the increased production of ketones due to the use of stored fat as an energy source. The phrase “intermittent fasting” may refer to any of the following:

Time-restricted eating
Alternate-day fasting
Periodic fasting (multi-day)

View fasting topic

Macronutrients

The three basic components of the human diet. Macronutrients are consumed in large quantities and provide necessary energy for the body. They include carbohydrates, fats, and proteins.

Melatonin

A hormone that regulates the sleep-wake cycle in mammals. Melatonin is produced in the pineal gland of the brain and is involved in the expression of more than 500 genes. The greatest influence on melatonin secretion is light: Generally, melatonin levels are low during the day and high during the night. Interestingly, melatonin levels are elevated in blind people, potentially contributing to their decreased cancer risk.^[1]

^ Feychting M; Osterlund B; Ahlbom A (1998). Reduced cancer incidence among the blind. Epidemiology 9, 5.

Postprandial

Relating to the period after eating. Postprandial biomarkers are indicators of metabolic function. For example, postprandial hyperglycemia is an early sign of abnormal glucose homeostasis associated with type 2 diabetes and is markedly high in people with poorly controlled diabetes.

Prediabetes

A health condition in which blood glucose levels are higher than normal, but not high enough to indicate a diagnosis of type 2 diabetes. Prediabetes can be halted or reversed with dietary and lifestyle modifications, including weight loss, exercise, and stress reduction.

Refined foods

Highly processed grains, starches, or sugars. Refined foods are typically processed via industrial extraction, concentration/purification, or enzymatic transformation and often lack the vitamins, minerals, and dietary fiber of whole foods. Many refined foods have a high glycemic index, which can rapidly produce an elevated glucose response.

View ultra-processed foods (upfs) topic

Time-restricted eating (TRE)

Restricting the timing of food intake to certain hours of the day (typically within an 8- to 12-hour time window that begins with the first food or non-water drink) without an overt attempt to reduce caloric intake. TRE is a type of intermittent fasting. It may trigger some beneficial health effects, such as reduced fat mass, increased lean muscle mass, reduced inflammation, improved heart function with age, increased mitochondrial volume, ketone body production, improved repair processes, and aerobic endurance improvements. Some of these effects still need to be replicated in human trials.

View sleep regularity topic

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